Obesity-associated oxidative stress: strategies finalized to improve redox state

Abstract

Obesity represents a major risk factor for a plethora of severe diseases, including diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. It is often accompanied by an increased risk of mortality and, in the case of non-fatal health problems, the quality of life is impaired because of associated conditions, including sleep apnea, respiratory problems, osteoarthritis, and infertility. Recent evidence suggests that oxidative stress may be the mechanistic link between obesity and related complications. In obese patients, antioxidant defenses are lower than normal weight counterparts and their levels inversely correlate with central adiposity; obesity is also characterized by enhanced levels of reactive oxygen or nitrogen species. Inadequacy of antioxidant defenses probably relies on different factors: obese individuals may have a lower intake of antioxidant- and phytochemical-rich foods, such as fruits, vegetables, and legumes; otherwise, consumption of antioxidant nutrients is normal, but obese individuals may have an increased utilization of these molecules, likewise to that reported in diabetic patients and smokers. Also inadequate physical activity may account for a decreased antioxidant state. In this review, we describe current concepts in the meaning of obesity as a state of chronic oxidative stress and the potential interventions to improve redox balance.

Figure 1

Mechanisms modulating oxidant/antioxidant balance in obesity. On the left-hand side are shown mechanisms underlying oxidative stress in obesity and obesity-associated complications, while on the right-hand side are shown strategies improving body antioxidant machinery (see text for details). Dotted lines: inhibitory effect. Solid lines: stimulatory effect. AGEs: advanced glycation end products; ATF: NF-κB, activating transcription factor; CPT2: carnitine palmitoyltransferase 2; CREB: cyclic AMP response element binding; ER: endoplasmic reticulum; FAS: fatty acid synthase; FoxO: forkhead box, sub-group O; HO-1: heme oxygenase-1; iNOS: inducible nitric oxide synthase; LPS: lipopolysaccharide MCP-1: monocyte chemotactic protein-1; miR: microRNA; NF-κB: nuclear factor-κB; Nox: NADPH oxidase; PKC: protein kinase C; PPAR-α: peroxisome proliferator-activated receptor-α; SCD1: stearoyl-CoA desaturase-1; SIRT: sirtuin; SREBP1: sucrose responsive element binding protein1; STAT3: signal transducer and activator of transcription 3; TGF-β: transforming growth factor-β; TNF-α: tumor necrosis factor-α.